Previous studies have demonstrated that the position of the dose-response curve for the discriminative stimulus (DS) effects of cocaine can depend upon training dose in both rats and monkeys. Pretreatment with the mu agonist morphine has been shown to shift the cocaine dose-response curve to the left under high- and low-dose training conditions in both species. A smaller dose of morphine was sufficient to achieve this effect after training with the low dose in rats. In monkeys, the kappa agonist U-50,488 has been shown to shift the cocaine dose-response curve to the right. In the present study, modulation of the DS effects of cocaine by U-50,488 was examined in rats trained to discriminate either 3 or 10 mg/kg cocaine from saline using a two-lever operant procedure. U-50,488 alone did not engender substantial cocaine-appropriate responses under either training condition. Responding was eliminated by 5.6 mg/kg. Pretreatment with 3 or 4.7 mg/kg U-50,488 attenuated the DS effects of cocaine under the low-dose, but not the high-dose, training condition. There was an approximate 2-fold increase in ED50 for cocaine. These findings indicate that, like morphine, the effects of U-50,488 can depend on the dose of cocaine used in discrimination training in rats. In addition, the influence of both drugs on the DS effects of cocaine are similar in rats and monkeys.